High-Sensitivity Enzyme Immunoassay for C-Reactive Protein in Dried Blood Spots

C-Reactive protein (CRP), the prototypical acute-phase protein, is produced by liver hepatocytes and regulated by cytokines, particularly interleukin-6 (1)(2). Circulating concentrations of CRP indicate inflammatory activity, and the recent development of highly sensitive CRP assays (3)(4)(5) has led to the discovery that slight increases in CRP (>1–2 mg/L) are indicative of low-grade inflammatory processes that may be related to the pathophysiology of cardiovascular disease. More than a dozen population-based studies have demonstrated that increased CRP is an independent risk factor for future cardiovascular disease, with adjusted odds ratios >2.0 (6)(7)(8)(9). The American Heart Association and the CDC have recommended measurements of CRP in clinical practice and called for additional population-based research (10). A potential obstacle to the measurement of CRP (as well as other biomarkers) in large epidemiologic, community-based studies is the requirement for venous blood. Venipuncture is a relatively invasive procedure that must be performed by a trained phlebotomist (usually in a clinical setting), and it requires readily accessible facilities where blood samples can be promptly processed and stored under controlled conditions. Assays using whole blood dried on filter paper may provide a viable alternative: Several community-based applications have shown this to be a convenient and reliable means to facilitate sample collection, storage, and transportation, and laboratory methods have been validated for a growing number of analytes (11)(12)(13)(14)(15)(16). “Guthrie papers” have been a core component of US hospital-based newborn-screening programs since the 1960s and are subject to a rigorous quality-control program (17). Samples can be collected on filter paper easily by nonmedical personnel: The patient’s finger is pricked with a sterile, disposable lancet (commonly used by diabetics), and up to five drops of blood (∼50 …